(291 days)
The Chloride test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care. Chloride measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of electrolyte and metabolic disorders.
The Creatinine test, as part of the epoc Blood Analysis System, is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of heparinized or un-anticoagulated arterial, venous or capillary whole blood in the laboratory or at the point of care. Creatinine measurements from the epoc Blood Analysis System are used in the diagnosis and treatment of certain renal diseases and in monitoring renal dialysis.
The epoc Blood Analysis System is an in vitro analytical system comprising a network of one or more epoc Readers designed to be used at the point of care (POC). The readers accept an epoc single use test card containing a group of sensors that perform diagnostic testing on whole blood. The blood test results are transmitted wirelessly to an epoc Host, which displays and stores the test results. The epoc System is intended for use by trained medical professionals as an in vitro diagnostic device for the quantitative testing of samples of whole blood. The test card panel configuration currently includes sensors for Sodium Na, Potassium K, Ionized Calcium iCa, pH, pCO2, pO2, Lactate, Glucose and Hematocrit Hct. This submission adds Chloride and Creatinine to this list of approved tests.
This medical device (epoc System) is an in vitro analytical system that provides diagnostic testing for various analytes in whole blood. This submission adds Chloride and Creatinine tests to its existing capabilities.
Here’s a breakdown of the acceptance criteria and supporting studies:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied through the comparison with predicate devices and established standards like CLSI recommendations. The reported device performance is presented in various non-clinical and clinical studies.
Chloride Test
| Acceptance Criteria / Performance Metric | Predicate Device (i-STAT™ Chloride) Target / Standard | epoc Chloride Test Performance |
|---|---|---|
| Intended Use | Diagnosis and treatment of electrolyte and metabolic disorders, including cystic fibrosis, diabetic acidosis, and hydration disorders. | Diagnosis and treatment of electrolyte and metabolic disorders. |
| Where Used | Hospital, point of care | Hospital, point of care |
| Sample Type | Venous, arterial, and capillary whole blood | Venous, arterial and capillary whole blood (heparinized or un-anticoagulated) |
| Reportable Range | 65 - 140 mmol/L | 65 - 140 mmol/L (supported by linearity study, Section 5.5.2) |
| Detection Principle | Ion selective membrane potentiometry | Ion selective membrane potentiometry |
| Sample Volume | 100 μL | At least 92 μL |
| Aqueous Precision (Total %CV) | (Implicitly comparable to predicate) | Level 1: 0.5%, Level 3: 0.7% (Figure 5.3) |
| Clinical Site (various users, all sites, control fluids): Level 1: 0.7%, Level 2: 0.6%, Level 3: 0.9% (Figure 5.14) | ||
| Whole Blood Precision (Avg. SD W-R / CV% W-R) | (Implicitly comparable to predicate) | Syringe: Normal: 0.63 / 0.6%, Spiked: 0.86 / 0.7% (Figure 5.10) |
| Capillary: Normal: 0.70 / 0.7%, Spiked: 1.11 / 0.9% (Figure 5.10) | ||
| Method Comparison (vs. Predicate/Comparator) | (Expected high correlation, low bias) | vs. non-POC Systems: R² = 0.96, Mean Bias at 112 mM = -1.3 (Figure 5.5) |
| vs. Abbott i-STAT: R² = 0.98, Mean Bias at 112 mM = -1.0 (Figure 5.5) | ||
| Various Matrices vs. i-STAT: R² ranges from 0.97 to 0.99 for venous, arterial, capillary (Figure 5.15), Avg. Bias at decision levels from -0.9 to 0.0 (Figure 5.16) |
Creatinine Test
| Acceptance Criteria / Performance Metric | Predicate Device (Roche Cobas c 511/512 CREP2) Target / Standard | epoc Creatinine Test Performance |
|---|---|---|
| Intended Use | Quantitative determination of creatinine in human serum, plasma, and urine for diagnosis of renal diseases. | Diagnosis and treatment of certain renal diseases and in monitoring renal dialysis. |
| Where Used | Hospital, laboratory | Hospital, point of care |
| Sample Type | Serum, Plasma, Urine | Venous, arterial and capillary whole blood (heparinized or un-anticoagulated) |
| Reportable Range | 0.03 - 30 mg/dL | 0.3 - 15.0 mg/dL (supported by linearity study, Slope 1.00, Intercept 0.07, R² 0.99 for 0.25 - 15.5 mg/dL, Section 5.5.2) |
| Detection Principle | Enzymatic cascade reaction (creatininase, creatinase, sarcosine oxidase) leading to peroxidase-catalyzed chromogenic peroxide detection. | Enzymatic cascade reaction (creatininase, creatinase, sarcosine oxidase) leading to amperometric peroxide detection. |
| Sample Volume | 2-5 μL | At least 92 μL |
| Aqueous Precision (Total %CV) | (Implicitly comparable to predicate) | Level 1: 4.9%, Level 3: 4.1% (Figure 5.3) |
| Clinical Site (various users, all sites, control fluids): Level 1: 6.8%, Level 2: 6.4%, Level 3: 6.3% (Figure 5.14) | ||
| Whole Blood Precision (Avg. SD W-R / CV% W-R) | (Implicitly comparable to predicate) | Syringe: Normal: 0.05 / 7.6%, Spiked: 0.06 / 3.9% (Figure 5.10) |
| Capillary: Normal: 0.04 / 6.8%, Spiked: 0.06 / 3.9% (Figure 5.10) | ||
| Method Comparison (vs. Predicate) | (Expected high correlation, low bias) | vs. Roche Cobas 6000: R² = 0.99, Mean Bias at 1.25 mg/dL = -0.06 (Figure 5.6) |
| Various Matrices vs. Roche Cobas: R² ranges from 0.99 for venous, arterial, capillary (Figure 5.15), Avg. Bias at decision levels from -0.04 to -0.08 (Figure 5.16) |
2. Sample Sizes Used for the Test Set and Data Provenance
Chloride Test:
- Method Comparison (Clinical Field Trials, Patient Samples):
- vs. non-POC Systems (Roche Cobas 6000, Siemens Advia): N = 96 (pooled venous samples, approximately equal numbers vs. each system). Data provenance not explicitly stated but implies clinical sites (hospitals).
- vs. Abbott i-STAT 300 (Predicate): N = 155 (patient samples, approximately equal numbers of venous, arterial, and capillary samples). Data provenance implies clinical sites (hospitals).
- Matrix Effects (Clinical Field Trials, Patient Samples):
- Venous: N = 49
- Arterial: N = 43
- Capillary: N = 63
- All: N = 155 (These are subsets of the Abbott i-STAT comparison data)
- Blood Precision (Clinical Sites, End Users):
- Chloride Blood Precision Site 1: 4 users, 10-10 replicates each for normal/spiked syringe samples. Total N around 80.
- Chloride Blood Precision Site 2: 8 users for syringe, 4 users for capillary. 10-11 replicates each. Total N around 220.
- Overall Blood Precision Summary:
- Normal Syringe: 120 tests (12 runs, 10 replicates)
- Spiked Syringe: 119 tests (12 runs, 10 replicates)
- Normal Capillary: 40 tests (4 runs, 10 replicates)
- Spiked Capillary: 40 tests (4 runs, 10 replicates)
- Anticoagulant Effect: 46 samples from a hospital, supplemented with 29 in-house samples.
- Provenance: Clinical field trials at two hospitals (patient samples), and in-house studies (aqueous precision, linearity, detection limit, analytical specificity, some anticoagulant effect evaluation). The data is a mix of prospective (patient samples collected in clinical field trials) and retrospective (in-house studies using prepared samples).
Creatinine Test:
- Method Comparison (Clinical Field Trials, Patient Samples):
- vs. Roche Cobas 6000 (Predicate): N = 144 (patient samples, approximately equal numbers of venous, arterial, and capillary samples). Data provenance implies clinical sites (hospitals).
- Matrix Effects (Clinical Field Trials, Patient Samples):
- Venous: N = 53
- Arterial: N = 42
- Capillary: N = 49
- All: N = 144 (These are subsets of the Roche Cobas comparison data)
- Blood Precision (Clinical Sites, End Users):
- Creatinine Blood Precision (multiple sites, multiple users): Each user performed 9-10 replicates for normal/spiked syringe and capillary samples. Total N is around 118 for syringe (normal and spiked), and around 30 for capillary (normal and spiked).
- Overall Blood Precision Summary:
- Normal Syringe: 118 tests (12 runs, 10 replicates)
- Spiked Syringe: 118 tests (12 runs, 10 replicates)
- Normal Capillary: 29 tests (3 runs, 10 replicates)
- Spiked Capillary: 30 tests (3 runs, 10 replicates)
- Anticoagulant Effect: 46 samples from a hospital, supplemented with 29 in-house samples.
- Provenance: Clinical field trials at a hospital site (patient samples), and in-house studies (aqueous precision, linearity, detection limit, analytical specificity, some anticoagulant effect evaluation). The data is a mix of prospective (patient samples collected in clinical field trials) and retrospective (in-house studies using prepared samples).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not explicitly state the number of experts used or their specific qualifications (e.g., "radiologist with 10 years of experience") for establishing ground truth for the test set. Instead, the "ground truth" or reference values for the clinical method comparison studies were established by:
- Predicate Devices: i-Stat™ Model 300 Portable Clinical Analyzer (for Chloride) and Roche Cobas c 511/512 CREP2 Creatinine Plus ver. 2 assay (for Creatinine). These are legally marketed devices that provide accepted reference measurements.
- Comparative Instruments/Laboratory Methods: Other non-point-of-care systems (e.g., Roche Cobas 6000, Siemens Advia for Chloride) and a serum-based laboratory method (for Creatinine) at clinical sites.
- Traceability: Both Chloride and Creatinine concentration values assigned to controls and calibrator fluids are traceable to NIST standards.
The expertise lies in the established and validated methodologies of these predicate and comparative devices/laboratory methods, rather than individual expert adjudication for each test case.
4. Adjudication Method for the Test Set
No explicit "adjudication method" in the sense of expert review for discrete cases (like 2+1, 3+1) is described. For in vitro diagnostic devices like this, the performance is typically evaluated by comparing the device's measurements against established reference methods (predicate devices or laboratory analyzers) which are considered the "ground truth." The statistical analysis (regression, bias, R²) serves as the method to determine agreement.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
An MRMC study, particularly in the context of human readers and AI assistance, is not applicable to this device. This is an automated in vitro diagnostic system that directly measures analytes in blood. There are no "human readers" interpreting images or data that AI would assist. The device itself performs the analysis, and the studies assess its accuracy, precision, and agreement with reference methods.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are essentially "standalone" performance evaluations of the device. The epoc Blood Analysis System is an automated system where the test card is inserted, blood is introduced, and analytical steps are performed automatically. The output is a direct measurement of analyte concentrations. The "human-in-the-loop" aspect primarily involves trained medical professionals collecting samples and operating the device, but not in interpreting raw data or making diagnostic decisions that the device's algorithm would assist. The performance data (precision, linearity, method comparison) reflects the device's inherent analytical capabilities.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for these studies is primarily:
- Reference Method Comparison: Measurements from legally marketed and established predicate devices (i-Stat™ for Chloride, Roche Cobas for Creatinine) and other validated laboratory methods (e.g., Roche Cobas 6000, Siemens Advia).
- Traceability to Standards: Calibration and control values are traceable to NIST (National Institute of Standards and Technology) standards (SRM 967 for Creatinine).
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI algorithms as the primary component of the device's measurement principle. The device relies on electrochemical sensors (ion-selective membrane potentiometry for Chloride, enzymatic cascade with amperometric detection for Creatinine).
However, in the broader sense of device development and calibration:
- In-house aqueous precision study: N=240 for Chloride (L1, L3) and N=239/241 for Creatinine (L1, L3) are mentioned (Figure 5.3). While these are presented as evaluation data, similar-sized or larger datasets would likely be used during initial development and calibration.
- Linearity study: Involved nine blood samples prepared from two pools, evaluated against an in-house standard method.
- The development and optimization of the enzymatic reactions and sensor response curves would involve extensive testing with many samples during the device's R&D phase, which functionally serves a "training" purpose for the device's internal calibration and algorithms. This specific data is not detailed as a distinct "training set" with a quantifiable size in this 510(k) summary.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" with specific ground truth establishment isn't explicitly detailed in the context of an AI/ML device. For a sensor-based diagnostic device like this, the "ground truth" for calibrating and optimizing the sensors (analogous to training) would be established through:
- NIST Traceability: Calibrator and control fluids are assigned values traceable to NIST standards. This is the ultimate ground truth for establishing the accuracy of the measurements.
- Reference Laboratory Methods: During development, the device would have been extensively correlated with established laboratory methods to ensure its measurements align with accepted clinical standards.
- Controlled Samples: Use of precisely prepared aqueous solutions, spiked blood samples, and pooled human serum with known concentrations, following guidelines like CLSI EP6-A and EP7-A2 for linearity, detection limits, and analytical specificity.
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.